The association between lipid metabolism gene polymorphisms and nephropathy in type 2 diabetes: a meta-analysis

Hyperlipidaemia has been identified as a risk factor for diabetic nephropathy via exacerbation of glomerular injury through the activation of multiple signaling pathways. This study's aim is to assess the associations between polymorphisms of genes involved in lipid metabolism, such as apolipoprotein E (ApoE), peroxisome proliferator-activated receptor gamma (PPAR gamma), acetyl-CoA carboxylase beta (ACACB), and type 2 diabetic nephropathy (T2DN). A search of the MEDLINE and Web of Science databases was used to identify relevant studies, and allele or genotype frequencies were pooled using fixed- or random-effects models. Forty-five studies were included in this meta-analysis, consisting of 10,920 type 2 diabetic patients with nephropathy and 16,203 type 2 diabetic patients without nephropathy. The OR for ApoE epsilon 2 versus epsilon 3 was 1.49 (95 % CI 1.13-1.95) in T2DN. The progression of T2DN was related to the presence of the epsilon 2 allele and epsilon 2 carrier with ORs of 1.72 (95 % CI 1.10-2.69) and 1.78 (95 % CI 1.18-2.69), respectively. The rs1801282 C > G variant in PPAR gamma presented a significant association with decreased T2DN risk, both in the G allele and GC/GG genotype with ORs of 0.77 (95 % CI 0.68-0.87) and 0.79 (95 % CI 0.69-0.92), respectively. The T allele in rs2268388 within ACACB showed an increased risk for T2DN, exhibiting an OR of 1.35 (95 % CI 1.12-1.63). Our meta-analysis supports that the ApoE epsilon 2 allele and ACACB rs2268388 C > T might act as promotion factors of nephropathy in type 2 diabetes, whereas PPAR gamma rs1801282 C > G is a promising candidate genetic variation for reducing susceptibility to T2DN.